Clinicians wrote 289 million opioid prescriptions in the United States in 2012, a 7.3% increase per capita from 2007, according to the U.S. Centers for Disease Control and Prevention (CDC). As the number of prescriptions has risen, so has opioid abuse, leaving physicians in the difficult and often stressful position of deciding which patients are appropriate candidates for opioid pain therapy.

Urine drug monitoring to detect drug abuse or diversion has become an important tool in that decision. A new CDC guideline published in April 2016 recommends clinicians test patients before beginning opioid therapy and at least annually thereafter (JAMA 2016;315:1624–45). Yet doctors often don’t know how to use or interpret urine drug tests. “Some clinicians don’t fully understand nor appreciate the limitations of laboratory testing and therefore can interpret results incorrectly,” said Paul Jannetto, PhD, co-director of the clinical and forensic toxicology laboratory at Mayo Clinic in Rochester, Minnesota.

In response to the challenges faced by clinicians and laboratory professionals in this area, AACC is releasing a new Laboratory Medicine Practice Guideline (LMPG) on how to monitor pain management patients. The recommendations will be presented at the 68th AACC Annual Scientific Meeting in Philadelphia. The guideline encourages laboratorians to become a resource for clinicians, according to Loralie Langman, PhD, co-director of the clinical and forensic toxicology laboratory at Mayo Clinic and chair of the LMPG committee. “We have several clinicians on our committee,” Langman said, “and they are more than willing to admit that there is generally a lack of understanding from their colleagues about which test to order, what things you can pick up, and what things you can’t pick up.”

Following the Evidence

Nancy Bratanow, MD, a pain specialist in Milwaukee, and a member of the LMPG committee, said the evidence-based nature of the guideline will help clinicians make better decisions, and also help them justify those decisions to regulators and payers. “The frequency of screening has been an issue recently,” Bratanow said. “Some people are so nervous they want to screen patients with every visit.” While some high-risk patients might need that, many do not. “With this guideline, they have some backup for what is actually helpful based on the literature,” she added.

The AACC LMPG recommends a urine drug screen before initiation of any controlled substance pain therapy and random drug testing at least once or twice a year for low-risk patients, and more frequently for high-risk patients, such as those with a history of substance abuse or addiction.

One of the most important new recommendations is that targeted, definitive testing should be used as a first-line test whenever possible, Langman said. Immunoassays are still clinically useful, according to the guideline, but clinicians must understand their limitations to avoid misinterpretation. Definitive tests, such as mass spectrometry-based assays, are more effective. “That is really the best type of test that could be ordered or used in this case, because it will provide clinicians with the specific information they need to know, as opposed to immunoassays which may only give you a general drug class,” said Jannetto, who is vice-chair of the LMPG committee.

Adulteration: The First Test

Another important recommendation is that urine adulterant testing be performed on all samples prior to analysis, and if adulteration is suspected no further testing should be performed on that sample, according to Langman. “There is no point in testing a sample that is not valid, because any results coming out of that sample will be useless,” she noted.

“That is a difference and change of practice,” Jannetto added, “because even when specimen validity testing is done, now you typically still perform all the other ordered tests and provide all the results back to the clinicians for them to decipher.” From a test utilization standpoint, it doesn’t make sense to test a sample that is not valid and could be interpreted incorrectly, he said.

The LMPG also divides drugs and drug metabolites into categories based on whether they should be tested routinely, only for high-risk patients, or only as clinically indicated. Jannetto hopes this will help counteract the marketing messages that encourage laboratories and clinicians to use panels with hundreds of analytes. “You don’t need to order every test on every patient,” he explained. “There’s no reason to order the world and use large, costly panels on every patient, which ultimately affects the entire healthcare system without offering significant benefit, especially for the low-risk patient.”

Collaboration Is Key

Daniel Carr, MD, a professor of public health and community medicine at Tufts University in Boston and president of the American Academy of Pain Medicine (AAPM), said he welcomes the AACC guideline, though he had not yet seen the draft. In particular, he supports the recommendation that clinicians collaborate with the laboratory. “There’s a certain working knowledge that clinicians carry around with them,” Carr said. “No matter how great their memory is and how much continuing medical education they receive, as individual fields get more and more complicated, they need to collaborate with their laboratory partners just because there’s a certain limit.”

Jeffrey Fudin, PharmD, president and director of scientific and clinical affairs at Remitigate LLC, has actually created software and a cell phone app to help clinicians interpret urine drug immunoassays. “The problem is, even the best-of-the-best and people who do this every day, like the pain doctors, don’t know how to interpret a lot of these tests,” Fudin said.

Fudin's software, called Urintel, helps clinicians solve the mystery of, for example, an 82-year-old woman in a wheelchair who tests positive for methadone. Urintel creates an automated, comprehensive electronic note to guide clinicians. This is important because misinterpretation of urine drug tests has caused honest patients to be kicked out of their pain clinics, Fudin said. Compounding problems for these patients, documented but misconstrued or inadequate notes in their medical charts makes it difficult for them to get an opioid prescription from any other doctor. “That’s a bad thing for the patient,” Fudin said. “It’s horrible.”

The CDC guideline also encourages clinicians to collaborate with the laboratory, noted Roger Chou, MD, a professor of medicine at Oregon Health and Science University in Portland and senior author of the CDC guideline. “Many primary care doctors aren’t all that familiar with which drugs they’re looking for,” Chou said. “For example, the synthetic opioids like methadone and fentanyl are actually not picked up on standard opioid immunoassays, so unless those are in your panel, you’ll get a negative urine test result.”

The difficulty in making recommendations, like those drafted by AACC, is the lack of randomized controlled studies that specifically address testing strategies, according to Chou. “It sounds like a noble effort but it is challenging because of the nature of the evidence,” he said.

Jannetto acknowledged there are not many well-controlled trials in this area, but said that the AACC LMPG is clear about the strength of evidence for each recommendation. The 11-member committee started a systematic review of thousands of academic papers in 2012, and updated it in 2015. After feedback from AACC members and the public, the guideline will pass through internal review with AACC and AAPM, and ultimately be submitted for publication.

The guideline highlights where more research is needed, Jannetto noted. “Upon revision, those gaps in the literature and science can be filled with well-designed studies that can then definitively answer those questions and provide even more concrete guidance to both clinicians and laboratory medicine professionals,” he said.